Substituted pyrrolo[2,1-f][1,2,4]triazines as FGFR inhibitors
Disclosed are an FGFR inhibitor and the use thereof in the preparation of a drug for treating FGFR-related diseases. In particular, disclosed are a compound as shown in formula (I) and a pharmaceutically acceptable salt thereof.
1. A compound of formula (I):
or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
R 1 is C 1-3 alkyl;
R 2 is C 1-3 alkyl;
X is H, F, Cl, Br, or I; and
Y is H, F, Cl, Br, or I.
2. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 1 is CH 3 or CH 2 CH 3 .
3. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 2 is CH 3 or CH 2 CH 3 .
4. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
X is H; and
Y is H.
5. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
X is F; and
Y is F.
6. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
X is Cl; and
Y is Cl.
7. The compound of claim 2 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 2 is CH 3 or CH 2 CH 3 .
8. The compound of claim 7 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
X is H; and
Y is H.
9. The compound of claim 7 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
X is F; and
Y is F.
10. The compound of claim 7 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
X is Cl; and
Y is Cl.
11. The compound of claim 1 , or a stereoisomer thereof, wherein the stereoisomer of the compound is of formula (I-1) or formula (I-2):
or a pharmaceutically acceptable salt thereof.
12. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof.
13. A method for inhibiting fibroblast growth factor receptor activity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof.
14. The method of claim 13 , wherein the subject has a disease caused by fibroblast growth factor receptor mutation or overexpression.
15. The method of claim 14 , wherein the disease caused by fibroblast growth factor receptor mutation or overexpression is selected from the group consisting of a solid tumor, gastric cancer, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma.
16. A method for inhibiting fibroblast growth factor receptor activity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 12 .
17. The method of claim 16 , wherein the subject has a disease caused by fibroblast growth factor receptor mutation or overexpression.
18. The method of claim 17 , wherein the disease caused by fibroblast growth factor receptor mutation or overexpression is selected from the group consisting of a solid tumor, gastric cancer, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma.
19. A compound, or stereoisomer thereof, wherein the stereoisomer of the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
20. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt or stereoisomer thereof.